Glyburide
(glye' bure ide).
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C23H28ClN3O5S 494.00

Benzamide, 5-chloro-N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]-sulfonyl]phenyl]ethyl]-2-methoxy-.
1-[[p-[2-(5-Chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclohex-ylurea [10238-21-8].
» Glyburide contains not less than 98.0 percent and not more than 102.0 percent of C23H28ClN3O5S, calculated on the dried basis.
Packaging and storage— Preserve in tight containers.
USP Reference standards 11
USP Glyburide RS Click to View Structure
Identification—
B: The chromatogram of the Assay preparation obtained as directed in the Assay exhibits a major peak for glyburide, the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparation, both relative to the internal standard, as obtained in the Assay.
Loss on drying— Dry it at 105 for 6 hours: it loses not more than 1.0% of its weight.
Residue on ignition 281: not more than 0.5%.
Chromatographic purity—
Mobile phase— Prepare as directed in the Assay.
Test solution— To about 10 mg of Glyburide, accurately weighed, add 10 mL of acetonitrile, and shake to dissolve. Add 4 mL of water, and mix.
Chromatographic system— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 2 mL per minute. Chromatograph the Test solution, and record the peak responses as directed for Procedure: the column efficiency is not less than 3500 theoretical plates.
Procedure— Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the areas for the major peaks. Calculate the percentage of each impurity in the portion of Glyburide taken by the formula:
100(ri / rs )
in which ri is the peak response for each impurity; and rs is the sum of the responses of all of the peaks: not more than 1.5% of any impurity, which elutes before glyburide, is found; not more than 0.5% of any other individual impurity is found; and not more than 2.0% of total impurities is found.
Assay—
Mobile phase— Dissolve 2.6 g of monobasic ammonium phosphate in 450 mL of water. Add 550 mL of acetonitrile, filter, and degas. Adjust, if necessary, with phosphoric acid or sodium hydroxide to a pH of 5.25 ± 0.30. Make adjustments if necessary (see System Suitability under Chromatography 621).
Internal standard solution— Dissolve progesterone in acetonitrile to obtain a solution containing about 0.2 mg per mL.
Standard preparation— To about 10 mg of USP Glyburide RS, accurately weighed, add 20.0 mL of Internal standard solution, and shake vigorously to dissolve. Add 4.0 mL of water, and mix.
Assay preparation— To about 10 mg of Glyburide, accurately weighed, add 20.0 mL of Internal standard solution, and shake vigorously to dissolve. Add 4.0 mL of water, and mix.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.4 for glyburide and 1.0 for progesterone; the resolution, R, between glyburide and progesterone is not less than 5.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the heights for the major peaks. Calculate the quantity, in mg, of C23H28ClN3O5S in the portion of Glyburide taken by the formula:
WS (RU / RS)
in which WS is the weight, in mg, of USP Glyburide RS taken to prepare the Standard preparation; and RU and RS are the peak height ratios obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Elena Gonikberg, Ph.D.
Principal Scientific Liaison
1-301-816-8251
(SM32010) Monographs - Small Molecules 3
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 3348
Pharmacopeial Forum: Volume No. 27(4) Page 2735